- Press Release Distribution

Genomic tug of war could boost cancer therapy

( Some patients with myelodysplastic syndromes, like acute myeloid leukemia, benefit from a chemotherapy drug called decitabine that stunts cancer growth. But many others are resistant to decatibine’s effects or become resistant over time. Wilmot Cancer Institute researchers have uncovered a “genomic tug of war” in animal studies that could influence how well certain patients—or certain cancers—respond to decitabine.

In a study published in the journal Development, Wilmot investigators found that decitabine causes different regions of DNA to engage in a tug of war for a gene activator, called H2A.Z. If too little of this gene activator is around, gene expression grinds to a halt, causing cells to die. However, many types of cancer have very high levels of H2A.Z, which may help them overcome this decitabine-induced tug of war, allowing the cancer to grow.

“Two years ago, we published a paper where we identified different subtypes of breast cancer based on the amount of H2A.Z in tumors,” said Patrick Murphy, PhD, assistant professor of Biomedical Genetics and Biology at the University of Rochester Medical Center and member of Wilmot’s Genetics, Epigenetics, and Metabolism program, who led the studies. “If our findings bear out in humans, we may be able to classify patients based on how much H2A.Z is in their tumor, and then decide whether or not this therapy is going to be more or less effective. So it could eventually be used alongside personalized medicine diagnostics.”

H2A.Z is a histone—a class of proteins that DNA wraps around. Different types of histones spool the DNA more tightly, keeping it protected, or loosely, allowing the DNA to be read and turned into proteins that carry out the many functions of a cell.

H2A.Z binds DNA loosely, helping to turn on nearby genes. For a long time, it was believed to only bind to regions of DNA that contain the code for proteins. However, Murphy and postdoctoral associate Fanju Meng, PhD, discovered that H2A.Z also binds to non-coding “junk DNA” in zebrafish.  

“That was when we first started wondering, maybe it's not doing what we think it's doing, or maybe it's doing something extra,” said Murphy. “We always thought of H2A.Z as a factor that goes to genes and helps turn them on. So when we started seeing it at different places, we started asking more questions.”

Research dating back to the early 2000’s has hinted at a murky link between H2A.Z and decitabine. More recent studies also show that decitabine can turn on portions of non-coding “junk DNA,” but those studies stopped short of explaining exactly how that happens.

Funded in part by a pilot award from URMC’s Environmental Health Science Center, Murphy and Meng tested the connection between decitabine and H2A.Z using zebrafish embryos. Treating the embryos with decitabine drew H2A.Z toward non-coding regions of DNA, reactivating them, and away from coding DNA, which curtailed gene expression, killed cells, and stunted embryo growth. In embryos that expressed high levels of H2A.Z—mimicking some cancers—there was enough H2A.Z to bind at both coding and non-coding regions and gene expression and embryo development were normal.

The same effect was seen with a toxic chemical, called TDCIPP, which is widely used in flame retardants and pesticides and has been found in human urine and breastmilk. The toxin caused H2A.Z to shift from coding to non-coding DNA regions, reducing gene expression and disrupting embryo development. But embryos that overexpressed H2A.Z were able to overcome the tug of war and were protected from the negative effects of the toxin.

“These external stressors—decitabine and TDCIPP—hijack essential aspects of cellular machinery to cause cell death,” said Murphy. “Our study identifies critical vulnerabilities which can be taken advantage of to improve future cancer therapeutics.”

Further research is needed, however, to confirm that this mechanism also happens in humans and to figure out how junk DNA sequences are able to hijack H2A.Z. As a first step in that direction, Murphy and Meng will soon study this mechanism in mouse embryonic stem cells—making the jump into mammals. 



New research questions the nature and meaning of "psychic-channeling" experiences

The question of disembodied consciousness or the afterlife has received much scientific scrutiny over the last several years. One line of research involves so-called "channelers" or mediums who claim to receive and communicate information that they believe comes from some other being or dimension of reality that differs from everyday reality. Now, an international team of scientists has critically examined these claims. New research published in the Journal of Scientific Exploration asked 15 pre-vetted channelers to access the same "nonphysical being or spirit" source and answer a structured set of 10 questions from the scientific team. The statistical ...

Drug manufacturers use FDA, patent strategies to keep insulin prices high

Drug manufacturers use FDA, patent strategies to keep insulin prices high
Over the last four decades, insulin manufacturers have extended their periods of market exclusivity on brand-name insulin products by employing several strategies, including filing additional patents on their products after FDA approval and obtaining many patents on delivery devices for their insulin products. That is the conclusion of a new analysis of FDA and patent records carried out by William Feldman of Brigham and Women’s Hospital, USA, and colleagues, and published November 16th in the open access journal PLOS Medicine. Insulin is the primary, life-saving treatment for type 1 and some type 2 diabetes but remains costly in the US even ...

Growing income inequities in the utilization of healthcare resources, Swedish study finds

Growing income inequities in the utilization of healthcare resources, Swedish study finds
Swedish people with the lowest incomes utilize primary and outpatient care on par with those with the highest incomes despite having significantly higher mortality rates, according to a new study published November 16th in the open access journal PLOS Medicine by Pär Flodin of Karolinska Institutet, Sweden, and colleagues. Socioeconomic differences in healthcare utilization have persisted in modern welfare states even with universal healthcare. In recent decades, Sweden has witnessed a rise in income inequalities, accompanied by shifts in the sociodemographic composition of the population ...

Love thy neighbor: Cooperation extends beyond one’s own group in wild bonobos

Love thy neighbor: Cooperation extends beyond one’s own group in wild bonobos
A new study published this week in Science challenges the notion that only humans are capable of forming strong and strategic cooperative relationships and sharing resources across non-family groups. Researchers from Harvard University and the German Primate Center examined the pro-social behavior of bonobos (Pan paniscus), one of humanity’s closest living relatives, finding that their cooperation extends beyond one’s own group to societal cooperation with different groups. Studying humans' two closest living relatives, chimpanzees and bonobos, can help reconstruct ancestral human traits like cooperation and conflict. Despite living in similar ...

New molecular glue degraders could help target troublesome proteins

Cells contain molecular machinery that targets and disposes of unwanted proteins to maintain homeostasis. Scientists think that with the help of “matchmaker” molecules called molecular glue degraders, this machinery could be hijacked to control proteins involved in diseases like cancer. But only a few of these glue degraders have been discovered so far—and mostly by chance. Zuzanna Kozicka, as a Ph.D. student at Friedrich Miescher Institute in Basel, Switzerland, embarked on a deliberate search for these glues with her team and identified a novel class of molecular glue degraders with more than 40 chemically diverse members. Kozicka, who is now a postdoctoral ...

High efficiency and cooling performance in an electrocaloric heat pump

Researchers have developed a solid-state electrocaloric cooling device that can generate a 20 kelvin temperature difference with high efficiency, according to a new study. The findings show that electrocaloric cooling can compete with other solid-state cooling strategies and offer a promising alternative to environmentally unfriendly vapor compression cooling. Cooling devices, including air-conditioning and heat pump systems, are estimated to consume roughly 20% of global electricity. Most of these systems operate through vapor-compression technologies, which are relatively inefficient and require environmentally harmful fluorinated refrigerants. Cooling through solid-state electrocaloric ...

The secret behind mussels’ quick-release interface

The same bundle of non-living filaments that mussels use to anchor themselves within their environment – to withstand crushing waves, for example – can also be jettisoned on demand. Mussels create this quick-release interface, a new study finds, by way of a neurochemically-mediated junction, where billions of motile cilia hold fast to interlinked biopolymer sheets. "[The study’s] findings could be informative about how nonliving materials can be dynamically interfaced with living tissue, as in the case of detachable biosensors and medical implants," write Guoqing Pan and Bin Li in a related ...

Presenting a new GRAB sensor toolkit for neuropeptides

New biosensors have helped reveal the activity of neuropeptides in the brain, researchers report, providing novel tools for studying the release, function, and regulation of these crucial signaling molecules in vivo. According to the study, the approach has the potential to address key questions regarding neuropeptides and their roles in health and disease. In the brain, neuropeptides are key signaling molecules in the body that regulate many critical physiological functions, including digestion, metabolism, sleep, and higher ...

UCSC doctoral graduate wins prestigious Science & SciLifeLab Prize for Young Scientists

UCSC doctoral graduate wins prestigious Science & SciLifeLab Prize for Young Scientists
Jessica Kendall-Bar, who received her Ph.D. in ecology and evolutionary biology last year from UC Santa Cruz with co-advisors Terrie Williams and Dan Costa, was named a recipient of the prestigious Science & SciLifeLab Prize for Young Scientists for her research on elephant seal sleep habits while they are at sea. The Science & SciLifeLab Prize is an international prize awarded by the American Association for the Advancement of Science (AAAS) and the journal Science to early career scientists for their outstanding thesis research in the life sciences. As ...

How cell identity is preserved when cells divide

CAMBRIDGE, MA -- Every cell in the human body contains the same genetic instructions, encoded in its DNA. However, out of about 30,000 genes, each cell expresses only those genes that it needs to become a nerve cell, immune cell, or any of the other hundreds of cell types in the body.   Each cell’s fate is largely determined by chemical modifications to the proteins that decorate its DNA; these modification in turn control which genes get turned on or off. When cells copy their DNA to divide, however, they lose half of these modifications, leaving the question: How do cells maintain the memory of what kind of cell they are supposed ...


Tracing how the infant brain responds to touch with near-infrared spectroscopy

These are the world's most effective charities

When is an aurora not an aurora?

Advisory panel issues field-defining recommendations for US government investments in particle physics research

Doctors discover many patients at UNC’s Inflammatory Bowel Disease Clinic screen positive for malnutrition

BNL: Advisory panel issues field-defining recommendations for U.S. government investments in particle physics research

International collaboration uses faculty member’s research on ancient Roman migration, seeks to understand Balkan genomic history

USF Health Heart Institute doctors are upbeat about cardiac regeneration

AI-driven breakthroughs in cells study: SFU-UBC collaboration introduces "MCS-detect" for advancements in super-resolution microscopy

Advisory panel issues field-defining recommendations for investments in particle physics research

$3.8 million NIH grant to fund Southwest Center on Resilience for Climate Change and Health

What happens when the brain loses a hub? 

Study reveals Zika’s shape-shifting machinery—and a possible vulnerability

RIT leading STEM co-mentoring network

Genetic mutations that promote reproduction tend to shorten human lifespan, study shows

CAMH develops potential new drug treatment for multiple sclerosis

Polyethylene waste could be a thing of the past

A dynamic picture of how we respond to high or low oxygen levels

University of Toronto researchers discover new lipid nanoparticle that shows muscle-specific mRNA delivery, reduces off-target effects.

Evolving insights in blood-based liquid biopsies for prostate cancer interrogation

Finding the most heat-resistant substances ever made

Time-tested magnesium oxide: Unveiling CO2 absorption dynamics

Engaging heterosexual men more effectively could slash HIV infections in Uganda

A fork in the rhod: Janelia researchers unveil comprehensive collection of rhodamine-based fluorescent dyes

The Gerontological Society of America congratulates new 2023 awardees

Texas A&M Institute part of national effort to harness nuclear laser fusion for limitless energy

How health system hesitancies contributed to COVID risks

Stand Up to Cancer names Julian Adams, Ph.D., President and CEO

Immersive VR goggles for mice unlock new potential for brain science

Racial and ethnic differences in hospice use among Medicaid-only and dual-eligible decedents

[] Genomic tug of war could boost cancer therapy